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1.
Environ Monit Assess ; 195(6): 769, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37249675

RESUMEN

Phosphogypsum (PG) is a by-product of phosphorus fertilizer that is typically stacked near production sites. Phosphogypsum contains trace elements and naturally occurring radioactive materials which may be hazardous to the surrounding environment. Phosphogypsum stack reclamation typically involves placing a soil cap and seeding grass to create a barrier for reducing environmental impacts; using woody species is uncommon. This study used three soil treatments with grass and woody species to determine whether mixing PG with soil affects soil chemical properties, and metal and radionuclide concentrations in tissue. None of the elements in soil was above Canadian guidelines for industrial land use. Aluminum, beryllium, chromium, copper, iron, magnesium, manganese, nickel, and vanadium were significantly higher in both study and reference sites than in pure PG; cadmium, calcium, fluoride, and strontium were significantly higher in pure PG. There was a poor correlation between soil and plant concentrations for most elements indicating trace elements were not in a bioavailable form. Trace elemental concentrations in plant tissue generally differed significantly with vegetation type but not within similar species. Trace elements and isotopes in PG were not high enough to affect plant growth. Among the isotopes, 222Ra emissions differed significantly with vegetation covers; activity of 226Ra in pure PG was above Canadian guidelines, but lower in vegetation tissue. This study suggests 15 cm soil mixed with PG can be used for PG stack revegetation when fast-growing Salix and Populus species are used in reclamation.


Asunto(s)
Oligoelementos , Oligoelementos/análisis , Suelo/química , Monitoreo del Ambiente , Canadá , Fósforo/análisis , Sulfato de Calcio/análisis , Plantas , Poaceae
2.
Neural Plast ; 2016: 9740353, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27247806

RESUMEN

Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L(-1) for male rats and 40 mg·L(-1) for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L(-1) NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L(-1) NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.


Asunto(s)
Líquido Cefalorraquídeo/metabolismo , Locomoción/fisiología , Aprendizaje por Laberinto/fisiología , Metaboloma/fisiología , Uranio/toxicidad , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Líquido Cefalorraquídeo/efectos de los fármacos , Femenino , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Metaboloma/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Uranio/administración & dosificación
3.
Artículo en Inglés | MEDLINE | ID: mdl-22884780

RESUMEN

Achieving an appropriate DHA status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how alpha-linolenic acid (ALA), provided for six weeks after weaning by different dietary fat matrix, improved brain DHA content of young male rats born from deficient-dams. The level of ALA achieved was based on the fat composition of usual infant vegetable formula. A palm oil-blend diet thus providing 1.5%ALA was compared to dairy fat-blend-based diets that provided either 1.5%ALA or 2.3%ALA, or a rapeseed oil diet providing 8.3%ALA (n-6/n-3 ratio were, respectively 10,10,5,2.5). The 1.5%ALA-dairy-fat-blend was superior to 1.5%ALA-palm-oil-blend to restore values of brain DHA, while the 2.3%ALA-dairy-fat-blend exhibited a further increase and reached the values obtained with pure rapeseed diet (8.3%ALA). Dairy-fat-blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of post-weaning rats. Providing dairy fat as well as a reduction of the LA/ALA ratio should be reconsidered to design infant formula.


Asunto(s)
Encéfalo/metabolismo , Productos Lácteos , Grasas de la Dieta/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Neurogénesis , Aceites de Plantas/metabolismo , Ácido alfa-Linolénico/administración & dosificación , Animales , Alimentos Fortificados/análisis , Glucolípidos/metabolismo , Glicoproteínas/metabolismo , Humanos , Lactante , Fórmulas Infantiles/química , Fórmulas Infantiles/metabolismo , Gotas Lipídicas , Masculino , Neuronas/metabolismo , Estado Nutricional , Ratas , Ratas Wistar , Regulación hacia Arriba , Destete , Ácido alfa-Linolénico/deficiencia , Ácido alfa-Linolénico/metabolismo , Ácido alfa-Linolénico/uso terapéutico
4.
Lasers Surg Med ; 39(10): 773-5, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18081148

RESUMEN

BACKGROUND AND OBJECTIVE: Hair removal around an ileo-colo ostomy can cause a number of problems. We compared laser hair removal with mechanical shaving around the ostomy. METHOD: Eleven patients were selected with hairy skin around the ostomy for therapy with an AlGaAs diode laser at 800 nm. Three to four treatments were given with an interval of 6 weeks. RESULTS: Ten patients completed laser therapy. The average hair reduction was 60% based on visual inspection. Shaving frequency reduced from once a week to once every 6 weeks. CONCLUSIONS: Laser hair removal likely becomes the preferred method in ostomy patients.


Asunto(s)
Remoción del Cabello/instrumentación , Láseres de Semiconductores , Terapia por Luz de Baja Intensidad , Estomía , Humanos , Proyectos Piloto , Resultado del Tratamiento
5.
N Engl J Med ; 356(12): 1235-40, 2007 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-17377161

RESUMEN

BACKGROUND: Although pulsed-dye-laser therapy is currently the gold standard for the treatment of port-wine stains, few objective data are available on its long-term efficacy. Using objective color measurements, we performed a 10-year follow-up of a previously conducted prospective clinical study of the treatment of port-wine stains with a pulsed-dye laser. METHODS: We invited the patients to undergo repeated color measurements performed by the same procedures as in the previous study. The results at long-term follow-up were compared with color measurements obtained before treatment and after completion of an average of five laser treatments of the complete port-wine stain. A questionnaire was used to investigate patients' satisfaction with the treatment and their perception of long-term changes in the stain. RESULTS: Of the 89 patients from whom color measurements were obtained in the previous study, 51 were included in this study. The patients had received a median of seven additional treatment sessions since the last color measurement, which had been made after an average of five treatments. The median length of follow-up was 9.5 years. On average, the stain when measured at follow-up was significantly darker than it was when measured after the last of the initial five laser treatments (P=0.001), but it was still significantly lighter than it was when measured before treatment (P<0.001). Fifty-nine percent of patients were satisfied with the overall treatment result. Six percent of patients reported that the stain had become lighter since their last treatment, 59% that it was unchanged, and 35% that it had become darker. CONCLUSIONS: Using objective color measurements, we observed significant redarkening of port-wine stains at long-term follow-up after pulsed-dye-laser therapy. Patients should be informed about the possibility of redarkening before beginning treatment.


Asunto(s)
Terapia por Luz de Baja Intensidad , Mancha Vino de Oporto/radioterapia , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Satisfacción del Paciente , Recurrencia , Pigmentación de la Piel , Encuestas y Cuestionarios
6.
Placenta ; 28(7): 611-5, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17098282

RESUMEN

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.


Asunto(s)
Líquido Amniótico , Transfusión Feto-Fetal/terapia , Hematócrito , Terapia por Luz de Baja Intensidad/efectos adversos , Modelos Biológicos , Anastomosis Arteriovenosa , Simulación por Computador , Femenino , Humanos , Embarazo
7.
Lasers Surg Med ; 31(5): 352-8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12430153

RESUMEN

BACKGROUND AND OBJECTIVES: The objective of this study was to compare the efficacy and safety of cryogen spray cooled laser treatment (CSC-LT) at wavelengths of 585 nm vs. 595 nm for port wine stain (PWS) birthmarks in a large series of patients. STUDY DESIGN/MATERIALS AND METHODS: A retrospective review was conducted of 64 patients with PWS treated with the ScleroPLUS [Candela (Wayland, MA)] pulsed dye laser (lambda = 585 or 595 nm wavelength; spot size 7 mm, tau(p) = 1,500 microseconds) over a 3-year period. Subjects' ages ranged between 3 months and 64 years; there were 42 females and 22 males, all of whom were Asian. Number of treatments ranged from 1 to 6. Duration of treatment ranged from 6 months to 2 years 11 months, with a mean of 12 months. Patients (n = 32) received CSC-LT (585 nm) using radiant exposures of 7-10 J/cm(2). A second group of patients (n = 32) received CSC-LT (595 nm) using radiant exposures of 7-10 J/cm(2). The primary efficacy measurement was the quantitative assessment of blanching response scores for CSC-LT (585 nm) versus CSC-LT (595 nm). Patients were monitored for adverse effects. RESULTS: Based on chi-squared analysis, there were clinical, and statistically significant, differences in blanching response scores favoring PWS receiving CSC-LT (585 nm) as compared to CSC-LT (595 nm) (P <.001). Transient hyperpigmentation was noted in 43.7% (n = 14) and 37.5% (n = 12) of patients in the CSC-LT (585 nm) and CSC-LT (595 nm) groups, respectively. In both groups, transient hyperpigmentation resolved in all patients within 1 year. Permanent hypopigmentation or scarring was not observed in either group. CONCLUSIONS: CSC-LT (585 nm) resulted in superior blanching as compared to CSC-LT (595 nm). Further study is required to optimize wavelength selection on an individual patient basis during PWS therapy in order to improve treatment results.


Asunto(s)
Cicatriz/etiología , Crioterapia/efectos adversos , Terapia por Luz de Baja Intensidad/efectos adversos , Trastornos de la Pigmentación/etiología , Mancha Vino de Oporto/radioterapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
8.
Holist Nurs Pract ; 13(3): 62-70, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10418387

RESUMEN

A systematic probability sample of 100 community-living older African-American women with chronic illnesses was evaluated during clinic visits to an urban safety-net hospital to explore health and demographic factors predictive of health-related hardiness (HRH). Questionnaires on HRH, function, self-assessed health, morbidity, health behavior, and selected demographics were used for collection of data. Multiple linear regression analyses ascertained that years of education and function explained 20% of the variance in HRH. Findings raise issues regarding validity of HRH prediction models and the cultural appropriateness of current methods of assessing HRH in older African-American women.


Asunto(s)
Adaptación Psicológica , Anciano/psicología , Actitud Frente a la Salud/etnología , Negro o Afroamericano/psicología , Enfermedad Crónica/psicología , Conductas Relacionadas con la Salud/etnología , Control Interno-Externo , Personalidad , Población Urbana , Mujeres/psicología , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Modelos Psicológicos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
9.
Lipids ; 28(7): 637-43, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8355593

RESUMEN

Because triacylglycerol (TAG) structure influences the metabolic fate of its component fatty acids, we have examined human colostrum and mature milk TAG with particular attention to the location of the very long chain polyunsaturated fatty acid on the glycerol backbone. The analysis was based on the formation of various diacylglycerol species from human milk TAG upon chemical (Grignard degradation) or enzymatic degradation. The structure of the TAG was subsequently deduced from data obtained by gas chromatographic analysis of the fatty acid methyl esters in the diacylglycerol subfractions. The highly specific TAG structure observed was identical in mature milk and colostrum. The three major fatty acids (oleic, palmitic and linoleic acids) each showed a specific preference for a particular position within milk TAG: oleic acid for the sn-1 position, palmitic acid for the sn-2 position and linoleic acid for the sn-3 position. Linoleic and alpha-linolenic acids exhibited the same pattern of distribution and they were both found primarily in the sn-3 (50%) and sn-1 (30%) positions. Their longer chain analogs, arachidonic and docosahexaenoic acids, were located in the sn-2 and sn-3 positions. These results show that polyunsaturated fatty acids are distributed within the TAG molecule of human milk in a highly specific fashion, and that in the first month of lactation the maturation of the mammary gland does not affect the milk TAG structure.


Asunto(s)
Calostro/química , Ácidos Grasos/análisis , Leche Humana/química , Triglicéridos/química , Femenino , Humanos , Hidrólisis
10.
Antiviral Res ; 19(3): 267-73, 1992 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1332606

RESUMEN

9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold better than PMEA against HSV-1, and equipotent against HIV and HCMV. The toxicity of 2 was studied in both resting and growing cells.


Asunto(s)
Adenina/análogos & derivados , Antivirales/síntesis química , Antivirales/farmacología , Organofosfonatos , Profármacos/síntesis química , Profármacos/farmacología , Adenina/síntesis química , Adenina/farmacología , Línea Celular , Citomegalovirus/efectos de los fármacos , Evaluación Preclínica de Medicamentos , VIH/efectos de los fármacos , Humanos , Simplexvirus/efectos de los fármacos
11.
Mol Pharmacol ; 41(1): 197-202, 1992 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1310143

RESUMEN

(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is an antiviral phosphonate nucleotide analogue that displays activity against a range of herpesviruses. Anion exchange high performance liquid chromatography analysis of the 60% methanol extract from [14C]HPMPC-treated cells reveals the formation of three major metabolites. Two of these were identified as phosphorylated forms of HPMPC, HPMPC phosphate, and HPMPC diphosphate, by liberation of HPMPC upon acid digestion and coelution with synthetic standards on high performance liquid chromatography. The third metabolite, which is resistant to alkaline phosphatase cleavage but sensitive to phosphodiesterase, is proposed to be an HPMPC phosphate adduct. In herpes simplex virus-1-infected cells the same three metabolites are detected, at concentrations comparable to those in uninfected cells. When HPMPC is removed from the medium, the concentrations of the metabolites in cells decrease slowly, with half-lives of approximately 6, 17, and 48 hr for HPMPC phosphate, HPMPC diphosphate, and the HPMPC phosphate adduct, respectively. HPMPC diphosphate inhibits herpes simplex virus-1 and -2 DNA polymerases with a lower Ki than that for DNA polymerase alpha, and enzyme inhibition is competitive in each case. The formation and the persistence of HPMPC phosphates in cells and the selective inhibition of viral DNA polymerases by HPMPC diphosphate can explain why cells pretreated with HPMPC remain refractory to viral infection even long after HPMPC is removed from the medium.


Asunto(s)
Antivirales/metabolismo , Citosina/análogos & derivados , Infecciones por Herpesviridae/metabolismo , Organofosfonatos , Compuestos Organofosforados/metabolismo , Animales , Radioisótopos de Carbono , Células Cultivadas , Cidofovir , Citosina/metabolismo , Infecciones por Herpesviridae/tratamiento farmacológico , Humanos , Cinética , Espectroscopía de Resonancia Magnética/métodos , Fosfatos/metabolismo , Fósforo
12.
Am J Clin Nutr ; 54(5): 829-35, 1991 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1951153

RESUMEN

The relationships between essential fatty acid (EFA) composition of colostrum and white adipose tissue (WAT) were examined on day 5 after delivery in 69 healthy women. Fatty acid composition was assessed by capillary gas chromatography, and 33 fatty acids were detected in colostrum and in WAT. Total polyunsaturated fatty acid (PUFA) content was similar in colostrum and in WAT (15.7 +/- 3.1% and 16.1 +/- 3.8%, respectively), but long-chain PUFA content was higher in colostrum than in WAT (2.9 +/- 0.6% and 1 +/- 0.2%, respectively; P less than 0.001). The concentrations of linoleic acid were significantly correlated between colostrum and WAT (r = 0.77, P less than 0.0001). No correlation was found for alpha-linolenic acid. The relationships between long-chain PUFA composition of colostrum and WAT suggested that individual factors along with tissue specificity of the mammary gland are involved in either the capacity of desaturating and chain-elongating pathways and/or incorporation of long-chain PUFAs into colostrum.


Asunto(s)
Tejido Adiposo/química , Calostro/química , Ácidos Grasos Esenciales/análisis , Triglicéridos/análisis , Ácidos Grasos Insaturados/análisis , Femenino , Humanos , Ácido Linoleico , Ácidos Linoleicos/análisis , Análisis de Regresión
13.
Med J Aust ; 153(3): 164-6, 1990 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-1974028

RESUMEN

This paper presents a case of Irukandji syndrome (envenomation by the jellyfish, Carukia barnesi) with pulmonary oedema and hypokinetic cardiac failure. This case highlights the need for victims (and operators of tours venturing into the waters of North Queensland) to treat even apparently innocuous stings with vinegar and to avoid freshwater bathing and rubbing of stings immediately after such incidents. It also reinforces the use of phentolamine to treat the symptoms of catecholamine release associated with the syndrome. This patient required inotropic support and further underlines the need for practitioners to be aware that the syndrome can have severe sequelae and that central venous monitoring and inotropic management should be available when treating Irukandji stings.


Asunto(s)
Mordeduras y Picaduras/complicaciones , Gasto Cardíaco Bajo/inducido químicamente , Cnidarios , Venenos de Cnidarios/envenenamiento , Escifozoos , Adulto , Animales , Femenino , Humanos , Edema Pulmonar/inducido químicamente , Queensland
14.
Antimicrob Agents Chemother ; 34(4): 637-41, 1990 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1693057

RESUMEN

Three analogs of thymidine, D4T [2',3'-didehydro-2',3'-dideoxythymidine; 1-(2,3-dideoxy-beta-D-glyceropent-2-enofuranosyl)thymine], FddT (3'-fluoro-3'-deoxythymidine), and AZT (3'-azido-3'-deoxythymidine), were compared in biological tests designed to assess their potential utility as anti-human immunodeficiency virus (HIV) agents. The in vitro potencies of these compounds against HIV infection in CEM cells were measured, with FddT and AZT being more potent than D4T. The cytotoxicities of D4T, FddT, and AZT for CEM cells were comparable. The triphosphates of these three derivatives inhibited purified HIV reverse transcriptase, and their affinities for this polymerase were found to be 1 or 2 orders of magnitude greater than that for the normal substrate, dTTP. D4T was less toxic than FddT or AZT for cultured human and mouse bone marrow cells (granulocyte-macrophage CFU). The three compounds had similar toxicities for human progenitor erythrocyte burst-forming units. In a 30-day mouse toxicity study, AZT and FddT produced a similar spectrum of hematopoietic toxicities. These toxic effects occurred at much lower doses of FddT than of AZT. At the higher doses of FddT, a significant incidence of lethality occurred. By contrast, D4T was considerably less toxic than both AZT and FddT in this study. The dose-limiting toxicity of D4T in mice was hepatotoxicity. The very different phosphorylation patterns of D4T, its lower toxicity, and its comparable potency relative to FddT and AZT suggest that the potential of D4T as an anti-HIV agent should be further explored.


Asunto(s)
Antivirales/uso terapéutico , Didesoxinucleósidos/uso terapéutico , VIH-1/efectos de los fármacos , Leucemia Experimental/tratamiento farmacológico , Zidovudina/uso terapéutico , Administración Oral , Animales , Antivirales/toxicidad , Médula Ósea/efectos de los fármacos , Didesoxinucleósidos/toxicidad , VIH-1/enzimología , Leucemia Experimental/sangre , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Retroviridae/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa , Estavudina , Zidovudina/toxicidad
15.
Blood ; 73(6): 1525-33, 1989 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-2713491

RESUMEN

The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate-limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women.


Asunto(s)
Coagulación Sanguínea , Factor VII/fisiología , Embarazo/sangre , Aniones , Frío , Ácidos Grasos/sangre , Femenino , Humanos , Técnicas In Vitro , Liposomas , Propiedades de Superficie
16.
J Med Chem ; 28(9): 1242-5, 1985 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2993615

RESUMEN

The synthesis of the thio analogue (thio-DHPG, 2) of 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described. The synthesis of 2 proceeded via the condensation of acetoxymethyl sulfide 9 with diacetylguanine 10 to give the protected nucleoside analogue 11. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 11 were successfully cleaved by an acetolysis reaction to furnish 14. Ammonolysis of 14 gave 2, which was also transformed to sulfoxide 15 and sulfone 16. Preliminary in vitro screening indicated that 2 exhibited comparable activity to DHPG against herpes simplex virus type 1 (HSV-1) but was less active against the type 2 virus (HSV-2) and human cytomegalovirus (HCMV). In a mouse encephalitis model (HSV-2), subcutaneous treatment with 2 led to a 53% reduction in mortality at a dose of 100 mg/kg per day.


Asunto(s)
Aciclovir/análogos & derivados , Herpes Simple/tratamiento farmacológico , Aciclovir/síntesis química , Aciclovir/farmacología , Aciclovir/uso terapéutico , Animales , Fenómenos Químicos , Química , Citomegalovirus/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Encefalitis/etiología , Femenino , Ganciclovir , Ratones , Simplexvirus/efectos de los fármacos
17.
Nouv Presse Med ; 8(25): 2083-8, 1979 Jun 07.
Artículo en Francés | MEDLINE | ID: mdl-471755

RESUMEN

The reaction of the body to inhaled mineral dust brings into play physiological and pathological mechanisms in which immunological processes may be involved. An analysis is made of phagocytosis by alveolar macrophages, of the transport of dust to the lymphatic system, of dust aggravation in lymphoid tissues on lymph glands and of the resulting lesions. The part played by dust in immunological disturbances is put forward in the cases of tubercular infections, experimental arthritis and tumors.


Asunto(s)
Polvo , Macrófagos/inmunología , Fagocitosis , Alveolos Pulmonares/inmunología , Animales , Artritis Experimental/inmunología , Carbono , Humanos , Neoplasias Pulmonares/inmunología , Sistema Linfático/inmunología , Neumoconiosis/inmunología , Alveolos Pulmonares/citología , Cuarzo , Ratas , Tuberculosis Pulmonar/inmunología
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